Recent advances in biology and medicine continuously bring new opportunities to basic, translational, and clinical research. New instrumentation and computational tools such as mass spectrometry are drivers behind these advances by delivering novel approaches to test hypotheses on potential biomarkers in normal and pathophysiological processes. In particular, singe and multiple reaction monitoring (SRM, MRM) now allow specific detection and quantification of target molecules in complex samples. Our long-term goal is to implement biomarker screening using multi-disciplinary research platforms to accelerate the development of new therapeutic, diagnostic, and predictive tools to improve the quality of the lives of people by treating and curing diseases. This proposal seeks support for a high resolution triple quadrupole mass spectrometer to accomplish this goal using SRMs and MRMs. Initially we will focus on Klotho, a specific protein involved in many normal and pathological processes related to a proinflammatory, oxidative stress environment. In collaboration with our colleagues at the BRIMS in Boston, we have developed a highly specific and highly sensitive Klotho h-SRM assay validated using plasma from patients with end-stage renal disease using the equipment requested in this application. With a developed and validated assay in hand, we can rapidly evaluate Klotho as a plasma biomarker in other indications. We will test the hypothesis that Klotho is dysregulated in patients with aging-related muscle loss (Major User, Urban) and cocaine addiction (Major User, Cunningham), two disease areas where we have already collected plasma samples. These projects take advantage of an existing assay being applied to a novel translational research setting focusing on Klotho as a high probability biomarker. Since we have the assay and samples, we only need the instrument to complete these studies. We will also establish an MRM assay in collaboration with the BRIMS group using existing patients'samples to validate a biomarker for diabetes risk-a polymorph mutation in ENPP1 (K121Q)-in a retrospective study (Major User, Abate). This is a unique approach to test the versatility of MRMs in biomarker screening in patients. Finally, we will develop MRMs for a panel of biomarkers to test in existing samples from patients with hepatocellular carcinoma (Major User, Elferink). We contend that the TSQ Vantage mass spectrometer requested in this application will advance our existing strengths in proteomics- based biomedical research at UTMB directed at improving clinical care. PUBLIC HEALTH RELEVANCE: Novel technical approaches using mass spectrometry have brought new abilities to basic, translational, and clinical research. The TSQ Vantage instrumentation requested in this application will directly impinge upon diagnosis and management of a variety of tragic chronic diseases including aging, drug addiction, diabetes, and cancer.